Design, Synthesis, and Biological Evaluation of Dual-Target Inhibitors of Acetylcholinesterase (AChE) and Phosphodiesterase 9A (PDE9A) for the Treatment of Alzheimer's Disease.
ACS Chem Neurosci
; 10(1): 537-551, 2019 01 16.
Article
en En
| MEDLINE
| ID: mdl-30252439
ABSTRACT
A series of dual-target AChE/PDE9A inhibitor compounds were designed, synthesized, and evaluated as anti-Alzheimer's Disease (AD) agents. Among these target compounds, 11a (AChE IC50 = 0.048 µM; PDE9A IC50 = 0.530 µM) and 11b (AChE IC50 = 0.223 µM; PDE9A IC50 = 0.285 µM) exhibited excellent and balanced dual-target AChE/PDE9A inhibitory activities. Meanwhile, those two compounds possess good blood-brain barrier (BBB) penetrability and low neurotoxicity. Especially, 11a and 11b could ameliorate learning deficits induced by scopolamine (Scop). Moreover, 11a could also improve cognitive and spatial memory in Aß25-35-induced cognitive deficit mice in the Morris water-maze test. In summary, our research developed a series of potential dual-target AChE/PDE9A inhibitors, and the data indicated that 11a was a promising candidate drug for the treatment of AD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acetilcolinesterasa
/
Inhibidores de la Colinesterasa
/
3',5'-AMP Cíclico Fosfodiesterasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
ACS Chem Neurosci
Año:
2019
Tipo del documento:
Article
País de afiliación:
China